Phenol derivatives and antitrypanosoma preventive/therapeutic agent comprising the same as active ingredient

Abstract

A compound represented by formula (I):[wherein, for example,X is a hydrogen atom or a halogen atom;R1 is a hydrogen atom;R2 is a hydrogen atom or a C1-4 alkyl group;R3 is —CHO or —COOH; andR4 is —CH═CH—(CH2)p—CH3 (wherein p is an integer of 1 to 12), —CH(OH)—(CH2)q—CH3 (wherein q is an integer of 1 to 13), —CH(OH)—CH2—CH(CH3)—(CH2)2—CH═C(CH3)2, —CH═CH—CH(CH3)—(CH2)3—CH(CH3)2, —(CH2)2—CH(CH3)—(CH2)3—CH(CH3)2 or —(CH2)8—CH3], an optical isomer thereof and a pharmaceutically acceptable salt thereof. These compounds have antitrypanosoma activity, and accordingly are useful as drugs for preventing or treating the diseases caused by trypanosoma.

Description

TECHNICAL FIELD[0001]The present invention relates to a novel halogen-containing phenol derivative having an alkyl side chain, an antitrypanosoma preventing / treating pharmaceutical composition having the same as an active ingredient, use of these components in producing a pharmaceutical composition for preventing or treating trypanosomiasis and a method of preventing or treating the diseases caused by Trypanosoma.BACKGROUND ART[0002]Onset of trypanosomiasis is caused by Trypanosoma protozoa and it is said that every year 200,000 to 300,000 of new patients of African sleeping sickness fall sick. At present the number of patients of African sleeping sickness cannot be confirmed due to the low reliability of the investigative data. According to the WHO, at least 150,000 people died of African sleeping sickness in 1996 and it is said that its aftereffect remains in not less than 100,000 people. Beyond that, enormous is the damage to domestic animals caused by a disease called as nagana,...

AI Technical Summary

Benefits of technology

The novel compounds exhibit significant inhibition of Trypanosoma brucei brucei respiration at lower concentrations than ascofuranone, with glycerin addition providing similar effects, demonstrating enhanced antitrypanosoma activity and safety.

Problems solved by technology

At present the number of patients of African sleeping sickness cannot be confirmed due to the low reliability of the investigative data.

Beyond that, enormous is the damage to domestic animals caused by a disease called as nagana, and several hundred thousands of cattle which are to be protein sources for people die every year.

Further, in the area of about 10,000,000 km2 of savanna equal to the United States of America, cattle-breeding is impossible due to Trypanosoma.

Thus, African sleeping sickness remarkably damages the health and the economical development of African people, and this is the reason why the WHO adopts the trypanosomiasis as one of the infectious diseases that should be controlled.

Particularly, the loss of cattle and horses is greatest and almost fetal, and they are led to anemia, edema, weakening and the like and fall dead in one month after infection.

However, these drugs are old and are gradually losing their efficacy.

Particularly, the resistance to melarsoprol of an arsenic agent causes a big problem and the situation is so dire that patients with no efficacy only await death and the development of novel antitrypanosoma agents are strongly desired.

Then, many researchers centered around Western countries have tried to develop drugs targeting this cyanide resistant oxidase but effective drugs having a selective toxicity have not been obtained.

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